Epilepsy is the commonest serious neurological disease, affecting 1.2% of the population in the UK. Epilepsy is often mistakenly viewed as easily treated, whereas, in fact, 40% of new-onset epilepsy remains uncontrolled after one year of antiepileptic drug (AED) treatment, and over 30% of people with epilepsy never respond to treatment, with consequent morbidity and mortality. Epilepsy is directly responsible for over 1000 deaths per year in the UK, and is the 5th most common cause of avoidable years of life lost in men and 8th in women. It is the leading cause of repeated unplanned admissions to NHS hospitals, and is estimated to cost the EU 15.5 billion euros per annum.
Currently, the diagnosis of epilepsy in a patient is usually based on a subjective interpretation by clinicians of descriptions of the seizure from the patient and witnesses, coupled with similarly subjective interpretation of features within EEG readings, MRI and CT scans, etc. In some instances, simultaneous video and EEG during prolonged recordings or using provocation may enable a seizure fortuitously to be directly observed, but simultaneous video-EEG is costly, not widely available, and fortuitously recording a seizure is unfeasible for most patients. Epilepsy is generally only considered as a diagnosis after a patient has suffered at least two attacks, and even after two or more attacks the diagnosis may remain uncertain, meaning that the prescription of anti-epileptic drugs is delayed. There are commercially available software packages which analyse data from prolonged EEG recordings and detect the presence of epileptiform spikes or seizures within this data. This allows clinicians reviewing the data to identify any epileptic events undergone by the patient which may not have had an external physical manifestation. This type of software is generally used for the monitoring of patients previously diagnosed with epilepsy, rather than as a diagnostic tool, and if used as a diagnostic would still require interpretation by a clinician of the events observed.
The assessment of the efficacy of anti-epileptic medication is essentially a trial-and-error process, with patients being prescribed what is thought to be an appropriate AED for the diagnosed epileptic syndrome, and then monitored for a decrease or cessation of seizures. If seizures continue without decrease, the patient must be prescribed a second AED and the process is repeated. Assessing treatment in this conventional manner means that patients can continue to have seizures for many months after initial diagnosis.
The clinical expression of seizures requires the involvement of large-scale brain networks, in order to create behavioural output and/or to allow subjective experience; since without behavioural or subjective features, there is no epilepsy. Seizures emerge rapidly from normal activity of brain networks and usually self-terminate; the timescale of onset and offset of a seizure is orders of magnitude faster than any plausible change in the numbers of neurons, axons, dendrites or synapses, and many other neuronal mechanisms. Therefore, the neuronal machinery causing seizures is the same machinery present in the brain interictally during normal function. The dynamic behaviour of a complex network is not predictable through studying the properties of individual small-scale components of the system. This means that the dynamic emergence of seizures in the complex system of the brain cannot be fully explained by studying, e.g. ion channels, individual neurons or brain slices.